Intravenous immunoglobulin in neurological disorders: a mechanistic perspective

Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over 25 years. It is a safe preparation with no long-term side effects. IVIg was first demonstrated to be effective in autoimmune disorders, two decades ago, in the treatment of acute immune thrombocytopenia. Since then, the therapeutic efficacy of IVIg has been established in Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis (MG), dermatomyositis (DM), Kawasaki syndrome and the prevention of graft-versus-host disease in recipients of allogeneic bone marrow transplants and reported in a large number of other autoimmune and systemic inflammatory conditions.     

Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies

BACKGROUND: The incidence of adefovir dipivoxil (ADV) nephrotoxicity has been previously reported with the 60 and 120 mg daily dose in human immunodeficiency virus (HIV). We report a complete analysis on the renal tolerance of ADV at the currently approved dose of 10 mg daily for the treatment of chronic hepatitis B. METHODS: To investigate the efficacy, safety, and the tolerability of two dosing regimens of ADV (10 mg daily or 30 mg daily), two double-blind, placebo-controlled studies were performed in patients with chronic hepatitis B and compensated liver disease who were not undergoing current treatment and who had evidence of hepatitis B virus (HBV) replication. RESULTS: There was no overall median change from baseline at week 48 in serum creatinine or serum phosphorus levels in the ADV 10 mg group. In the ADV 30 mg group there was a slight increase of 0.2 mg/dL in median serum creatinine levels, and decrease of 0.1 mg/dL in serum phosphorus levels at week 48. Serum creatinine increase and hypophosphatemia were more frequently observed in patients receiving ADV 30 mg daily compared with ADV 10 mg and placebo. There were no grade 4 proteinuria, hematuria, or glycosuria events. CONCLUSION: Mild nephrotoxicity was demonstrated with the dose of 30 mg daily. Nephrotoxicity, as defined by an increase >/=0.5 mg/dL from baseline in serum creatinine or a serum phosphorus value of <1.5 mg/dL on two consecutive occasions, was not observed in patients treated with ADV 10 mg for a median follow-up period of approximately 64 weeks.     

Does Robotic Adrenalectomy Improve Patient Quality of Life When Compared to Laparoscopic Adrenalectomy?

The purpose of this study was to evaluate and compare perioperative quality of life in patients after laparoscopic versus robotic adrenalectomy. From November 2000 through August 2003, 33 consecutive patients underwent laparoscopic (n = 14) and robotic (n = 19) adrenalectomy. Data were obtained prospectively during management and by patient questionnaire (SF36, State-Trait Anxiety Inventory) preoperatively and postoperatively, at day 4 and at 6 weeks. Physical functioning, role limitations due to physical health problems, and bodily pain (Physical SF36 scores) were decreased at day 4 (p = 0.004) in all patients when compared to preoperative levels; and became similar to preoperative levels after 6 weeks. Patients who underwent robotic adrenalectomy had an increased score at 6 weeks of role limitations due to emotional problems (Mental SF36 score) (p = 0.03). No other significant difference was observed between patients after laparoscopic or robotic adrenalectomy. Although state anxiety was decreased postoperatively at day 4 and at 6 weeks (p = 0.01) in all patients, there was no significant difference between laparoscopic and robotic adrenalectomy. Postoperative pain was similar in both groups but had a tendency to be higher when patients underwent a left adrenalectomy (p = 0.07). Similarly, state anxiety had a tendency to be higher postoperatively at day 4 in patients after left adrenalectomies (p = 0.06). This study provides an evaluation of perioperative quality of life in patients after minimally invasive (laparoscopic and/or robotic) adrenalectomy. We observed no major difference between patients who underwent laparoscopic or robotic adrenalectomy. Thus, patients perioperative quality of life is not a justifiable parameter on which to base promotion of robotic adrenalectomies.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14-17th, 2004.     

Long-term durability of resection and end-to-end anastomosis for ascending aortic aneurysms

BACKGROUND: Ascending aortic aneurysms with normal sized sinotubular junction are generally treated by resection of the dilated aorta and replacement with tubular graft. Aortic resection and direct end-to-end anastomosis has been applied to repair aortic coarctation, interrupted aortic arch, and traumatic aortic rupture. No data exist regarding the long-term durability of this approach in ascending aortic aneurysms. The aim of this case-control study was to illustrate the durability of this operation by presenting our entire experience and the long-term follow up of a cohort of 34 patients who underwent ascending aortic aneurysm resection and primary end-to-end anastomosis between January 1990 and March 2003 in Caen University Hospital (Caen, France). METHODS: The mean age of patients was 61.5 +/- 12.5 years, and there were 18 male and 16 female patients. The operative technique included extensive mobilization of the arch, supra-aortic trunks, and inferior vena cava to enable approximation of the aortic ends, thus avoiding tension on the suture lines. Associated aortic valve replacement was performed in 27 patients; mechanical valves were used in 19. A bicuspid aortic valve was present in 9 patients; in 3 cases the valve was regurgitant. Aortic valve regurgitation was present in a total of 7 patients. Patients were followed up at regular intervals; total follow-up was 2187 patient-months, with a median follow-up time of 72 months per patient (25th-75th percentile 10.5-102.7 months). RESULTS: One patient died 10 days after the operation of aortic rupture related to suture infection caused by mediastinitis. Late deaths occurred in 3 patients, who died 12, 62, and 71 months after the operation, but none of these deaths were attributable to late aortic repair failure. No patient in this series required reoperation, including patients with aortic regurgitation or bicuspid aortic valve. Follow-up was 91.1% complete at the closing date of April 1, 2003. The Kaplan-Meier estimate of survival for all patients was 120.4 months (95% confidence interval 105.1-135.7 months). The median of preoperative maximal aortic diameter was 55.1 mm (range 50.3 to 67.5 mm, 25th-75th percentile 50.5-56.8 mm). The median immediate postoperative diameter was 40.3 mm (range 33.4-46.4 mm, 25th-75th percentile 37.2-42.0 mm, P <.0001 relative to preoperative diameter), and the median length of the resected aortic segment was 52 mm (range 48-76 mm, 25th-75th percentile 50.1-66.4 mm). The median decrease of aortic diameter was 24.9 mm (range 8.9-32.6 mm, 25th-75th percentile 18.2-26.6 mm).The median aortic diameter at the end of the follow-up was 41.0 mm (range 34.6-46.1 mm, 25th-75th percentile 37.0-43.2 mm, P =.6 relative to immediate postoperative diameter). CONCLUSIONS: Ascending aorta aneurysm resection and primary end-to-end anastomosis provides effective long-term outcome and in selected cases represents a good alternative to aortic interposition grafting. Aortic regurgitation and bicuspid aortic valve do not represent a contraindication for this treatment.     

Fluorescent bronchoscopy

Detection of clinically occult lung neoplasms may represent an opportunity for early curative intervention. Fluorescent bronchoscopy is a sensitive technique for detecting early endobronchial tumors that may be combined with CT scanning as part of a comprehensive lung cancer screening program. Identification and longitudinal follow-up of dysplastic endobronchial changes with fluorescent bronchoscopy should facilitate studies of chemoprevention and further knowledge regarding the natural history of these lesions. Analysis of bronchial epithelium with novel techniques such as genomic hybridization and gene expression arrays might provide even better predictors of progression of dysplastic endobronchial lesions.     

MUC6 is a marker of seminal vesicle-ejaculatory duct epithelium and is useful for the differential diagnosis with prostate adenocarcinoma

The diagnosis of prostate adenocarcinoma is usually made on needle biopsies. Numerous benign lesions may mimic malignancy, especially when the focus of carcinoma is limited. The presence of seminal vesicle-ejaculatory duct epithelium on prostate biopsy is not rare and could cause confusion with adenocarcinoma. Lipochrome pigments are frequently encountered in seminal vesicle-ejaculatory duct but may be also seen in prostate adenocarcinoma. Prostate specific antigen immunostaining in difficult cases is sometimes used, but high-grade adenocarcinomas may be negative. In one previous report, MUC6 was found to be expressed in seminal vesicle but not in normal prostate. MUC6 belongs to the family of human mucin genes. So we investigated herein the immunohistochemical expression of MUC6 in prostate adenocarcinomas and seminal vesicle-ejaculatory duct. We have tested 30 prostate adenocarcinomas of various grade, 10 normal seminal vesicles, and 10 prostate adenocarcinomas invading the seminal vesicles. The tissues were fixed in 10% buffered formalin and embedded in paraffin. Immunohistochemistry was performed using the avidin-biotin-peroxidase complex technique. All adenocarcinomas and normal prostate structures tested were negative. In contrast, all seminal vesicles were diffusely immunostained with MUC6 antibody. We concluded that MUC6 is a valuable marker of seminal vesicle-ejaculatory duct and is useful for the differential diagnosis with prostate adenocarcinoma.     

Neural timing of visual implicit categorization

Most of the neuroimaging studies that have shown visual category-specific activations or categorization effects have been based on a subtractive approach. In the present study, we investigated, by means of EEG, not only the net result of the categorization but also the dynamics of the process. Subjects had to perform a target detection task throughout an image set of distractors belonging to six categories: letters, geometrical figures, faces, tools, structured textures and Asiatic characters. Multivariate analyses were performed on the responses to the non-target stimuli according to their category. Categorical neural responses were only obtained on P2 latencies and N2 amplitudes. This result suggests that there are no differences in the first stage of the implicit categorization of the distractors (visual analysis and proximal stimulus representation elaboration from 100 to 220 ms) and that differences appear between 220 and 280 ms (matching to structural representations). Over-learned stimuli (e.g. letters) elicited the shortest P2 latency, contrasting with unknown categories (e.g. Asiatic characters) that revealed the longest P2 latencies and flattened N2 waves. Categorical differences indicate that the more a subject knows about an object, the less cognitive resources are used. In conclusion, our results suggest that a reduction in neural activity could reflect an improved accuracy in cognitive and cortical processing.     

Differential distribution of tight junction proteins suggests a role for tanycytes in blood‐hypothalamus barrier regulation in the adult mouse brain

The median eminence is one of the seven so‐called circumventricular organs. It is located in the basal hypothalamus, ventral to the third ventricle and adjacent to the arcuate nucleus. This structure characteristically contains a rich capillary plexus and features a fenestrated endothelium, making it a direct target of blood‐borne molecules. The median eminence also contains highly specialized ependymal cells called tanycytes, which line the floor of the third ventricle. It has been hypothesized that one of the functions of these cells is to create a barrier that prevents substances in the portal capillary spaces from entering the brain. In this paper, we utilize immunohistochemistry to study the expression of tight junction proteins in the cells that compose the median eminence in adult mice. Our results indicate that tanycytes of the median eminence express occludin, ZO‐1, and claudin 1 and 5, but not claudin 3. Remarkably, these molecules are organized as a continuous belt around the cell bodies of the tanycytes that line the ventral part of the third ventricle. In contrast, the tanycytes at the periphery of the arcuate nucleus do not express claudin 1 and instead exhibit a disorganized expression pattern of occludin, ZO‐1, and claudin 5. Consistent with these observations, permeability studies using peripheral or central injections of Evans blue dye show that only the tanycytes of the median eminence are joined at their apices by functional tight junctions, whereas tanycytes located at the level of the arcuate nucleus form a permeable layer. In conclusion, this study reveals a unique expression pattern of tight junction proteins in hypothalamic tanycytes, which yields new insights into their barrier properties. J. Comp. Neurol. 518:943–962, 2010. © 2009 Wiley‐Liss, Inc.